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Title: Copper-Catalyzed C(sp3)–H Methylation via Radical Relay
The methyl moiety is a key functional group that can result in major improvements in the potency and selectivity of pharmaceutical agents. We present a radical relay C–H methylation methodology that employs a β-diketiminate copper catalyst capable of methylating unactivated C(sp3)–H bonds. Taking advantage of the bench-stable DABAL-Me3, an amine-stabilized trimethylaluminum reagent, methylation of a range of substrates possessing both activated and unactivated C(sp3)–H bonds proceeds with a minimal amount of overmethylation. Mechanistic studies supported by both experiment and computation suggest the intermediacy of a copper(II) methyl intermediate reactive toward both the loss of the methyl radical as well capture of radicals R• to form R–Me bonds.  more » « less
Award ID(s):
2303206
NSF-PAR ID:
10489486
Author(s) / Creator(s):
; ; ;
Publisher / Repository:
American Chemical Society
Date Published:
Journal Name:
ACS catalysis
ISSN:
2155-5435
Format(s):
Medium: X
Sponsoring Org:
National Science Foundation
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